Inflammatory markers as predictors of active labor onset among nulliparous women

描述（由申请人提供）：分娩护理提供者通常的目标是在“活动性”分娩开始时，即预期宫颈扩张率增加时，将产妇送入产房。然而，活产只能根据扩张随时间的变化来回顾性判断。报告表明，大约一半的正常收缩，低风险，无产妇女在主动分娩前入院。这些妇女在分娩过程中更容易接受干预，包括与主动分娩的妇女相比，剖宫产的风险增加了两倍以上。这些数据表明需要额外的标准来更准确地确定入院前的分娩状态。越来越多的证据表明，分娩的发生和进展是由炎症事件介导的，随着分娩的进展，生殖组织和母体血液中的炎症生物标志物越来越多地被检测到。本研究的目的是确定炎症生物标志物是否有助于预测活动性分娩的发生。据推测，随着时间的推移，特定炎症生物标志物的增加可以预测因自然分娩而入院的低风险、未分娩妇女（n = 200）的主动扩张状态（平均在分娩后4小时内> 0.5 cm/hr）。描述性比较设计将用于评估特定炎症生物标志物(即白细胞（WBC）计数、血清促炎细胞因子（IL-12、IL-6、IL-8、TNF-1）、c反应蛋白（CRP）的变化率之间的关联；体温随时间的变化以及入院后4小时内宫颈扩张的量。炎症生物标志物将在分娩入院时测量，并在2小时和4小时后再次测量。将评估的特定炎症生物标志物随时间的变化包括入院->入院+2小时、入院->入院+4小时和入院->入院+2小时->入院+4小时。个体炎症生物标志物在数据收集时间点之间的变化幅度将用于构建预测主动分娩的ROC曲线。根据生物标志物变化的幅度，将进行逻辑回归分析，并将劳动分类作为因变量，即主动或不主动扩张。入院时宫颈扩张和几种常见的分娩干预措施将被纳入模型协变量。同时运行多种炎症生物标志物的模型也将被考虑。如果炎症生物标志物随时间的急性变化与主动分娩有关，这些生物标志物可用于决定“何时”让分娩妇女进入产房。最大限度地增加积极分娩的妇女人数是改善分娩结果的重要一步。这项研究的结果将用于为基于生理的分娩评估方案的制定提供信息，旨在最大限度地增加在主动分娩时或开始后入院的妇女人数。后续研究还将确定临床干预对分娩相关炎症介质的影响。

DESCRIPTION (provided by applicant): Labor care providers typically aim to admit a laboring woman to the labor unit at the onset of "active" labor, i.e., when the rate of cervical dilation is anticipated to increase. However, active labor can only be determined retrospectively based on changes in dilatation over time. Reports indicate that approximately one-half of regularly contracting, low-risk, nulliparous women are admitted for labor prior to active labor. These women are more prone to intervention during labor including a more than two-fold risk of cesarean delivery compared to women admitted in active labor. These data suggest that additional criteria are needed to more accurately determine labor state prior to admission. Evidence increasingly suggests that labor onset and progression is mediated by inflammatory events and inflammatory biomarkers become increasingly detectable in reproductive tissues and maternal blood as labor advances. The purpose of this study is to determine if inflammatory biomarkers may assist in predicting active labor onset. It is hypothesized that increases in specific inflammatory biomarkers over time can predict an actively dilating state (> 0.5 cm/hr, on average, over the first 4 hrs after labor admission) among low-risk, nulliparous women admitted for spontaneous labor onset (n = 200). A descriptive, comparative design will be used to evaluate the association between rates of change in specific inflammatory biomarkers [i.e., white blood cell (WBC) count, serum pro-inflammatory cytokines (IL-12, IL-6, IL-8, TNF-1), C-reactive protein (CRP); and body temperature] over time and the amount of cervical dilation during the first 4 hrs post-admission. Inflammatory biomarkers will be measured at labor admission and again 2 hrs and 4 hrs later. Specific inflammatory biomarker changes over time that will be evaluated include admission -> admission+2hrs, admission -> admission+4hrs, and admission -> admission+2hrs -> admission+4hrs. The magnitude of change in individual inflammatory biomarkers between data collection time points will be used to construct ROC curves with respect to the prediction of active labor. Logistic regression analyses, based on the magnitude of biomarker change, will be performed with classification of labor as the dependent variable, i.e., actively or not actively dilating. Cervical dilatation at admission and several common labor interventions will be included as model covariates. Models running multiple inflammatory biomarkers simultaneously will also be considered. If acute changes in inflammatory biomarkers over time are associated with active labor onset, these biomarkers could be used when making decisions regarding "when" to admit laboring women to the labor room. Maximizing the number of women admitted in active labor is an important step toward improving labor outcomes. Findings from this study will be used to inform the development of a physiology-based labor assessment protocol aimed at maximizing the number of women admitted at or after the onset of active labor. Subsequent studies will also determine the effects that clinical interventions have on labor-associated inflammatory mediators. PUBLIC HEALTH RELEVANCE: Inflammatory events are implicated in initiating labor and propagating its progression. The measurement of inflammatory biomarkers may, therefore, be predictive of active labor onset which, at present, can only be determined retrospectively - often hours after a decision to admit for labor has already been made. Approximately one-half of regularly contracting, low-risk, nulliparous women are admitted for labor prior to active labor and women in this high-volume group are more prone to intervention during labor including a more than two-fold risk of cesarean delivery compared to women admitted in active labor. If acute changes in inflammatory biomarkers over time validly predict active labor onset, their measurement can be used to maximize the number of women admitted in active labor. More positive short- and long-term labor outcomes should follow.